PTAB

IPR2025-01353

Guardant Health Inc v. Cold Spring Harbor Laboratory

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Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Varietal counting of nucleic acids for obtaining genomic copy number information
  • Brief Description: The ’510 patent discloses methods for determining genomic copy number information from a DNA sample. The technology purports to overcome "amplification distortion"—biases introduced during polymerase chain reaction (PCR)—by using unique molecular tags that allow for the accurate counting of original nucleic acid molecules present in a sample.

3. Grounds for Unpatentability

Ground 1: Claims 1, 2, 9-11, 22, 26, 28, and 33-34 are obvious over Lo in view of McCloskey, Brenner, Chee, and Porreca

  • Prior Art Relied Upon: Lo (Application # 2009/0029377), McCloskey (a 2007 journal article), Brenner (Patent 7,537,897), Chee (Patent 9,085,798), and Porreca (Patent 11,840,730).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the primary reference, Lo, taught the majority of steps in independent claim 1, including obtaining nucleic acid segments from a sample, assigning sequenced reads to a genomic location by mapping, and obtaining relative copy number information by counting the mapped reads. However, Petitioner contended that Lo did not explicitly teach the critical intervening steps of (b) randomly tagging the initial nucleic acid molecules with unique tags, (c) amplifying them via PCR, and (d) sequencing the resulting tagged molecules. Petitioner asserted this missing technique—using molecular tags to enable accurate molecule counting despite amplification distortion—was a well-known solution to a known problem and was explicitly taught by the combination of secondary references McCloskey, Brenner, Chee, and Porreca.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSITA) would combine Lo’s counting method with the tagging techniques because amplification bias was a well-understood issue in quantitative sequencing. Petitioner argued that applying the known solution of molecular tagging to improve the accuracy of Lo’s counting-based method was an obvious step to solve a known problem. Furthermore, several of the secondary references were cited as expressly contemplating the use of tagging for copy number variation analysis, making the combination a natural and predictable convergence of known technologies to achieve an improved result.
    • Expectation of Success: A POSITA would have had a high expectation of success in combining these teachings. Petitioner asserted that the methods for designing, synthesizing, and attaching molecular tags were routine and well-established prior to the patent's priority date. This was supported by arguments that the patent’s own inventor had admitted in a separate scientific publication that using tags to facilitate molecular counting was "not a new idea."

Ground 2: Dependent Claims are obvious over Lo and Secondary References

  • Prior Art Relied Upon: Lo (Application # 2009/0029377) in view of various combinations of McCloskey, Brenner, Chee, and Porreca.

  • Core Argument for this Ground:

    • Prior Art Mapping: Petitioner extended its primary obviousness argument to numerous dependent claims by asserting their additional limitations recited other well-known techniques or obvious design choices.
      • For claims requiring sample tags for multiplexing (claims 5-7), Petitioner pointed to teachings in Brenner and McCloskey of "indexing" and "batch-stamps" to pool and simultaneously analyze multiple patient samples.
      • For claims defining uniqueness by a combination of the tag and the genomic sequence (claims 12, 23), Petitioner cited teachings in Brenner, Chee, and Porreca showing this was a known method to allow for smaller tag libraries.
      • For claims requiring specific tag structures, such as having constant and variable portions of different lengths (claims 15, 17, 26, 28), Petitioner argued this was a common tag design disclosed in the secondary references to simplify workflow by combining primer binding sites (constant) with unique identifiers (variable).
    • Motivation to Combine: The motivations for adding these features were presented as routine optimizations for efficiency and cost-effectiveness. For example, multiplexing with sample tags reduces sequencing costs, and defining uniqueness by the tag-DNA combination allows for the use of smaller, less complex tag libraries. Petitioner framed these modifications as predictable choices from a finite number of known options available to a POSITA.

  • Additional Grounds: Petitioner asserted additional obviousness challenges for claims 18-21 and 29-32 based on the use of tags constructed from limited nucleotide palettes (e.g., using only dinucleotides or trinucleotides), arguing these represented obvious design choices to simplify tag synthesis and downstream data analysis.

4. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-12, 15, 17-23, 26, and 28-36 of Patent 12,234,510 as unpatentable.